de Barros Mariel, Mota da Silva Luisa, Boeing Thaise, Somensi Lincon Bordignon, Cury Benhur Judah, de Moura Burci Ligia, Santin José Roberto, de Andrade Sérgio Faloni, Monache Franco Delle, Cechinel-Filho Valdir
Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil.
Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade Federal do Paraná (UFPR), Centro Politécnico, Jardim das Américas, 81531-970, Curitiba, PR, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2016 Apr;389(4):403-17. doi: 10.1007/s00210-015-1208-0. Epub 2016 Jan 13.
Solidago chilensis Meyenmost (Asteraceae), popularly known as "Brazilian arnica" or "arnica-do-campo," is widely used in the folk medicine to treat gastric disorders. Based on this, the gastroprotective activity of S. chilensis methanolic extract was investigated. Besides, a phytochemical study allowed isolation of two flavonoids (quercitrin and afzelin). The gastroprotective effects were investigated in acute gastric ulcer models, and the antisecretory activity was assessed in vivo and in vitro. The adhered mucus levels, reduced glutathione (GSH) content and myeloperoxidase (MPO) activity were quantified in ulcerated tissues. The contribution of isolated compounds in extract effects was evaluated, and its doses were calculated according to its yield. To evaluate the in vivo healing properties of S. chilensis methanolic extract, a chronic gastric ulcer was induced in mice by 10 % acetic acid. Evaluation of tumor necrosis factor (TNF) levels was also performed at the site of the acetic acid-induced gastric ulcer. In parallel, effects on cell viability and cell proliferation of fibroblasts (L929 cells) were determined by in vitro trials. Firstly, the S. chilensis methanolic extract (100 or 300 mg/kg) reduced the ulcer area induced by ethanol/HCl in mice when compared to the vehicle group. Moreover, the S. chilensis extract (300 mg/kg) prevented the mucus depletion, the increase in MPO activity and the decrease in the GSH levels in the ulcerated gastric tissue. The S. chilensis extract also was able to decrease the indomethacin-induced gastric ulcer in rats at a dose of 100 mg/kg. The antisecretory effect of the extract (100 mg/kg, intraduodenal (i.d.)) was confirmed by the reduction in the volume and acidity in parallel to an increase in the pH of gastric content. In addition, quercitrin (1.38 mg/kg, but not 0.46 mg/kg) and afzelin (0.026 and 0.078 mg/kg) decreased the ethanol/HCl-induced gastric ulcer. In this model, quercitrin (1.38 mg/kg) prevented the depletion of gastric GSH content and both quercitrin (1.38 mg/kg) and afzelin (0.078 mg/kg) reduced the MPO activity. These compounds also inhibited the H(+),K(+)-ATPase activity at a concentration of 1-100 μg/ml. In addition, the participation of quercitrin and afzelin in these effects also was confirmed. Furthermore, after 4 days of the treatment, an oral administration of S. chilensis methanolic extract (100 mg/kg) reduced the area of the gastric ulcer induced by acetic acid and the regeneration of the gastric mucosa was accompanied by a reduction in gastric TNF levels. The healing properties of the extract also were confirmed by enhancement of proliferation and coverage of scratched wounds in a fibroblast monolayer. Together, our results confirmed the gastroprotective effect of S. chilensis methanolic extract as well as its gastric healing potential and provided some support to the traditional use of S. chilensis for prevention and treatment of gastric lesions in complementation to its known anti-inflammatory properties.
智利一枝黄花(菊科),俗称“巴西山金车”或“田野山金车”,在民间医学中广泛用于治疗胃部疾病。基于此,对智利一枝黄花甲醇提取物的胃保护活性进行了研究。此外,通过植物化学研究分离出了两种黄酮类化合物(槲皮苷和阿夫泽林)。在急性胃溃疡模型中研究了其胃保护作用,并在体内和体外评估了其抗分泌活性。对溃疡组织中的黏附黏液水平、还原型谷胱甘肽(GSH)含量和髓过氧化物酶(MPO)活性进行了定量。评估了分离出的化合物在提取物作用中的贡献,并根据其产率计算了剂量。为了评估智利一枝黄花甲醇提取物的体内愈合特性,用10%乙酸诱导小鼠患慢性胃溃疡。还在乙酸诱导的胃溃疡部位评估了肿瘤坏死因子(TNF)水平。同时,通过体外试验确定了其对成纤维细胞(L929细胞)活力和细胞增殖的影响。首先,与赋形剂组相比,智利一枝黄花甲醇提取物(100或300mg/kg)减少了乙醇/盐酸诱导的小鼠溃疡面积。此外,智利一枝黄花提取物(300mg/kg)可防止溃疡胃组织中黏液耗竭、MPO活性增加和GSH水平降低。智利一枝黄花提取物还能够以100mg/kg的剂量减少吲哚美辛诱导的大鼠胃溃疡。提取物(100mg/kg,十二指肠内(i.d.))的抗分泌作用通过胃内容物体积和酸度的降低以及pH值的升高得到证实。此外,槲皮苷(1.38mg/kg,但不是0.46mg/kg)和阿夫泽林(0.026和0.078mg/kg)减少了乙醇/盐酸诱导的松胃溃疡。在该模型中,槲皮苷(1.38mg/kg)可防止胃GSH含量的耗竭,并且槲皮苷(1.38mg/kg)和阿夫泽林(0.078mg/kg)均降低了MPO活性。这些化合物还在1-100μg/ml的浓度下抑制H(+),K(+)-ATP酶活性。此外,还证实了槲皮苷和阿夫泽林参与了这些作用。此外,治疗4天后,口服智利一枝黄花甲醇提取物(100mg/kg)可减少乙酸诱导的胃溃疡面积,胃黏膜的再生伴随着胃TNF水平的降低。提取物的愈合特性还通过成纤维细胞单层中划痕伤口增殖和覆盖的增强得到证实。总之,我们的结果证实了智利一枝黄花甲醇提取物的胃保护作用及其胃愈合潜力,并为智利一枝黄花在预防和治疗胃部病变方面的传统用途提供了一些支持,以补充其已知的抗炎特性。